Teaching Old Drugs New Tricks

Pharmaceutical research is associated with high costs, both in terms of time and money. In the last year, drugs with a value of over $20 billion have come off patent, meaning many pharma giants face a crisis in their late-stage product pipeline. This, in addition to the high risks involved in getting a drug to market, encourages maximal exploitation of drugs already proven safe.

It is becoming increasingly difficult for the giant pharmaceutical companies to maintain their success. The delivery of blockbuster drugs to sustain their growth offers enormous challenges, yet is required to nourish the colossal budgets associated with the very risky business of pharmaceutical R&D. The major threats to a drug in development are twofold; first, that the drug lacks clinical efficacy, and second, that it displays unsuitable characteristics, such as an unacceptable side-effect profile. Although there are a few exceptions (for example, thalidomide, where the sideeffects were associated with a distinct population), often little is done with these failed drugs.

To name just one failure in the later stages of clinical development (Phase III), Pfizer’s anti-hypercholesterolemia drug, torcetrapib, was terminated due to adverse side-effects – by which time some $800 million had been spent on the project with little to no chance of return. Worryingly for the pharmaceutical industry, up to two thirds of drugs in clinical development fail due to safety issues.

Given this high failure rate of drugs (see Figure 1), maximising the revenue from drugs that are already marketed perhaps offers a new take on the famous mantra of the Nobel Prize-winning pharmacologist, Sir James Black, “The most fruitful basis for the discovery of a new drug is to start with an old drug.” This lifecycle management of marketed drugs has essentially two approaches:

1. Extend the exclusivity period of a successful drug by, for example:

• Identifying an advantageous reformulation
• Broadening the patient population (inclusion of children, for example)
• Extending the drug use to related indications (for example, further subtypes of depression)